The role of conformational entropy in molecular recognition by calmodulin

Michael S. Marlow, Jakob Dogan, Kendra K. Frederick, Kathleen G. Valentine, A. Joshua Wand

Research output: Contribution to journalArticle

191 Scopus citations

Abstract

The physical basis for high-affinity interactions involving proteins is complex and potentially involves a range of energetic contributions. Among these are changes in protein conformational entropy, which cannot yet be reliably computed from molecular structures. We have recently used changes in conformational dynamics as a proxy for changes in conformational entropy of calmodulin upon association with domains from regulated proteins. The apparent change in conformational entropy was linearly related to the overall binding entropy. This view warrants a more quantitative foundation. Here we calibrate an 'entropy meter' using an experimental dynamical proxy based on NMR relaxation and show that changes in the conformational entropy of calmodulin are a significant component of the energetics of binding. Furthermore, the distribution of motion at the interface between the target domain and calmodulin is surprisingly noncomplementary. These observations promote modification of our understanding of the energetics of protein-ligand interactions.

Original languageEnglish (US)
Pages (from-to)352-358
Number of pages7
JournalNature chemical biology
Volume6
Issue number5
DOIs
StatePublished - May 2010

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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